Cardiopulmonary arrest (CA) is a frequent critical care emergency. Recently the role of resuscitation of the central nervous system (CNS) following CA has received increasing attention. Post CA CNS damage is an important factor in the death of many of the 60% of all patients who die in the hospital following initially "successful" resuscitation. The present therapy for post-CA brain damage is at best empirical. The goal of this project is to utilize a proven model system for induction of total cerebral ischemia (TCI) to investigate the pathophysiological mechanisms which underlie the microcirculatory abnormalities documented post-TCI in the earlier studies in this laboratory. The intervention protocols will be aimed both at exploring the pathophysiologic mechanisms in post-arrest brain damage and at ameliorating the residual neurologic damage seen in this model system following TCI. The model will evaluate hemodynamic variables, sequential neurologic examinations and sequential regional cerebral blood flows (RCBF) determinations using the radioactive microsphere technique. Intervention protocols to be evaluated, in addition to a 10 minute TXI control group receiving prolonged intenive care unit/respiratory support, include: a) high dose barbiturate therapy, b) vasodilator therapy (phenotolamine, prostacycline), c) cyclo-oxygenase inhibition with indomethacin, d) calcium ionophore antagonist therapy. The parameters which directly effect RCBF, including pCO2, will be kept constant or varied individually (e.g., mean arterial pressure with vasodilator therapy may decrease). Light microscopy will be used to evaluate the severity of ischemic neuronal damage in chronic control and chronic treatment animals. In the final phase, the optimal regime developed in the animal model experiments will be assessed in a clinical study of patients with neurologic damage following CA in the medical intensive care unit at University Hospitals.